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. 2022 Dec 21:13:988538.
doi: 10.3389/fmicb.2022.988538. eCollection 2022.

Genetic characterization and molecular epidemiology of Coxsackievirus A12 from mainland China during 2010-2019

Qin Guo  1   2 , Hehe Zhao  1 , Yong Zhang  1   3 , Xianjun Wang  4 , Qiuli Yu  5 , Zhaolin Tan  6 , Huanhuan Lu  1 , Jinbo Xiao  1 , Tianjiao Ji  1 , Shuangli Zhu  1 , Dongyan Wang  1 , Qian Yang  1 , Zhenzhi Han  1 , Wenbo Xu  1 , Dongmei Yan  1
Affiliations

Genetic characterization and molecular epidemiology of Coxsackievirus A12 from mainland China during 2010-2019

Qin Guo et al. Front Microbiol. .

Abstract

Coxsackievirus A12 (CVA12) is an enterovirus that has been isolated in many countries in recent years. However, studies on CVA12 are limited, and its effective population size, evolutionary dynamics and recombination patterns have not been clarified now. In this study, we described the phylogenetic characteristics of 16 CVA12 strains isolated from pediatric HFMD patients in mainland China from 2010 to 2019. Comparison of the nucleotide sequences and amino acid sequences with the CVA12 prototype strain revealed that the 16 CVA12 strains are identical in 78.8-79% and 94-94.2%, respectively. A phylodynamic analysis based on the 16 full-length VP1 sequences from this study and 21 sequences obtained from GenBank revealed a mean substitution rate of 6.61 × 10-3 substitutions/site/year (95% HPD: 5.16-8.20 × 10-3), dating the time to most recent common ancestor (tMRCA) of CVA12 back to 1946 (95% HPD: 1942-1947). The Bayesian skyline plot showed that the effective population size has experienced twice dynamic fluctuations since 2007. Phylogeographic analysis identified two significant migration pathways, indicating the existence of cross-provincial transmission of CVA12 in mainland China. Recombination analysis revealed two recombination patterns between 16 CVA12 strains and other EV-A, suggesting that there may be extensive genetic exchange between CVA12 and other enteroviruses. In summary, a total of 16 full-length CVA12 strains were reported in this study, providing valuable references for further studies of CVA12 worldwide.

Keywords: Coxsackievirus A12; enteroviruses; evolutionary dynamics; foot and mouth disease; hand; phylogenetic analysis; recombination.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Phylogenetic analysis based on the full-length VP1 sequences of 16 CVA12 from this study and 21 sequences retrieved from the GenBank. Bootstrap values greater than 70% were highlighted. The 16 CVA12 strains from this study are represented by black dots.
Figure 2
Figure 2
(A) A phylogenetic tree with Maximum Clade Credibility (MCC) was constructed based on the full-length VP1 sequences of CVA12 in GenBank and 16 CVA12 sequences from this study. The blue bar represents 95% HPDs of tMRCAs. (B) A Bayesian skyline plot based on the full-length VP1 sequences of CVA12 reflects the effective population size in mainland China from 2009 to 2019.
Figure 3
Figure 3
Spatial spread links of CVA12 between sampling locations in Mainland China. The figure shows only the state transitions with supported BF ≥ 3 and posterior mean value ≥0.5. Red arrow, Very strongly supported rates with BF ≥ 100.
Figure 4
Figure 4
Neighbor-joining phylogenetic trees of (A) VP1, (B) P1, (C) P2 and (D) P3 were constructed based on 16 CVA12 strains from this study and EV-A prototype strains. The 16 CVA12 strains from this study are represented by a diamond, and CVA12 prototype strain is represented by a circle. The numbers on these nodes indicate the bootstrap support for that node (the percentage of 1000 bootstrap replicates). The scale bars indicate the genetic distance.
Figure 5
Figure 5
Recombination events of CHN_SD_2015_81 and CHN_HN_2019_214 strains were investigated based on Similarity plots and bootscanning analyses. Panels (A,C) are the similarity diagram, and Panels (B,D) are the guided scan analysis. CHN_SD_2015_81 and CHN_HN_2019_214 strains were used as query sequences (shown in black font).
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